CD1 displays its own negative regulators

After two decades of the study of lipid antigens that activate CD1-restricted T cells, new studies show how autoreactive & alpha;& beta; T-cell receptors (TCRs) can directly recognize the outer surface of CD1 proteins in ways that are lipid-agnostic. Most recently, this lipid agnosticism has turned to negativity, with the discovery of natural CD1 ligands that dominantly negatively block autoreactive & alpha;& beta; TCR binding to CD1a and CD1d. This review highlights the basic differences between positive and negative regulation of cellular systems. We outline strategies to discover lipid inhibitors of CD1-reactive T cells, whose roles in vivo are becoming clear, especially in CD1-mediated skin disease.

Automated summary

Studies show that autoreactive αβ T-cell receptors can directly recognize the outer surface of CD1 proteins in a lipid-agnostic manner, which is contrary to the previous understanding of lipid antigens activating CD1-restricted T cells. Recently, natural CD1 ligands have been discovered that dominantly negatively block autoreactive αβ T-cell receptor binding to CD1a and CD1d. This review highlights the differences between positive and negative regulation of cellular systems and outlines strategies to discover lipid inhibitors of CD1-reactive T cells, especially in CD1-mediated skin disease.